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Biomedical subjects

V Sharma

Publications and source records attributed to V Sharma.

At least 235 records · Page 13Linked to original sources

Effect of C lambda-C kappa domain switching on Fab activity and yield in Escherichia coli: synthesis and expression of genes encoding two anti-carbohydrate Fabs.

We have used a strategy of hybrid gene synthesis and constant domain shuffling to construct and functionally express in Escherichia coli genes encoding two anti-carbohydrate Fabs, one specific for a Brucella cell-surface polysaccharide and the second for the human blood group A determinant. Very similar VL amino acid sequences made possible the simultaneous synthesis of the two corresponding genes. A class switching approach was used in Fd and light chain gene assembly. The two independently synthesized VH genes were fused to a previously made sequence encoding the C(gamma 1)1 domain as an alternative to synthesis of the natural C gamma 2b 1 and C mu 1 sequences. The VL genes were initially coupled to a synthetic C kappa gene. When these light chain and the above Fd genes, each preceded by the ompA signal sequence, were expressed from two-cistron DNA, yields of functional periplasmic Fab were low and, in each instance, limited by light chain availability. Replacement of the C kappa domains with a C lambda 1 domain resulted in a significant increase in the amount of soluble periplasmic light chain and functional Fab for both the Brucella and blood group A antibodies. The C kappa and C lambda 1 forms of each of the Brucella and blood group A Fabs, with His5 fusions at the C-termini of the Fd chains, were purified by immobilized metal affinity chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Heterotopic pregnancy obtained after in-vitro fertilization and embryo transfer following bilateral total salpingectomy: case report.

Heterotopic (coexistent ectopic and intra-uterine) pregnancy is common following in-vitro fertilization and multiple embryo transfer. Total bilateral salpingectomy is generally considered to eliminate the risk of ectopic, and hence heterotopic pregnancy. This is, however, not strictly correct as it does not eliminate the risk of interstitial tubal pregnancy. This is the first reported case of a heterotopic pregnancy following total bilateral salpingectomy. The diagnostic pitfalls and a suggested method of avoiding them are discussed.

Adult↗

Serotonergic function in aggressive and nonaggressive boys with attention deficit hyperactivity disorder.

OBJECTIVE: This study was designed to assess central serotonergic (5-HT) function in aggressive and nonaggressive boys with attention deficit hyperactivity disorder. METHOD: Prolactin response to a challenge dose of the 5-HT agonist d,l-fenfluramine was assessed in 25 7-11-year-old boys with attention deficit hyperactivity disorder who were divided into aggressive and nonaggressive subgroups. In addition, the subgroups were compared on plasma catecholamine metabolites and platelet 5-HT. RESULTS: The aggressive group had a significantly greater prolactin response to the fenfluramine challenge than the nonaggressive subgroup. The groups did not differ on peripheral measures of neurotransmitter function. CONCLUSIONS: These data suggest that aggressive and nonaggressive children with attention deficit hyperactivity disorder differ in central 5-HT functioning.

Aggression↗

Development and validation of a scale for rating mood states of psychiatric inpatients.

OBJECTIVE: The authors assessed reliability and validity of a scale developed for use with inpatients on a mood disorders unit. The scale is used to rate a patient's mood along a quantitative continuum from -5, depressive stupor, through 0, euthymic, to 5, full mania. The scale lists behaviors that constitute criteria for each rating point. Mixed states and idiosyncratic behavior can also be assessed. METHODS: Assessment of the scale's reliability and validity was based on data for 53 psychiatric inpatients. The scale's reliability was assessed by comparing nurses' ratings. Validity was assessed by comparing nurses' ratings with patients' self-ratings using previously validated self-report instruments as well as a patient self-report version of the scale. RESULTS: Interrater reliability for the instrument was high (r = .84). Estimates of validity obtained using patient self-report measures ranged from .54 to .85. CONCLUSIONS: The psychometric properties of the scale are comparable to and in some cases are superior to those reported for instruments that include more items and that take longer to complete.

Adult↗

Human B cell interleukin 10.

Interleukin 10 (IL-10) is a novel lymphokine which exhibits strong DNA and amino acid sequence homology to BCRF1, an open reading frame in the Epstein-Barr virus genome. Using a wide panel of EBV positive and EBV negative cell lines, it has been shown that EBV positive B cell lines derived from patients with AIDS and Burkitt's lymphoma (AABCL) secrete large quantities of B cell IL-10, compared with EBV-positive B cell lines obtained from patients with undifferentiated lymphomas of Burkitt's and non-Burkitt's types. In contrast, EBV-negative B cell lines do not express IL-10 by Northern blot analysis, ELISA or even PCR. B cell IL-10 is confined to a narrow window in the B cell differentiation pathway, and whereas IL-10 expression is detected in mature and preplasmacytic stages, none of the pro-B, pre-B, or myeloma cell lines produce IL-10. EBV exerts direct effect on the production of B cell IL-10, and purified tonsillar B cells infected with EBV were triggered to secrete IL-10. The large amount of IL-10 secreted by B cells derived from AIDS-related lymphomas suggests that HIV-1 also exerts direct effect on IL-10 secretion. B cell IL-10 may function as autocrine growth factor for B cell lymphomas, and both IL-10 and BCRF1 seem to be involved in the pathophysiology of non-Hodgkin's lymphomas.

Amino Acid Sequence↗

Cognitive deterioration from long-term abuse of dextromethorphan: a case report.

Dextromethorphan (DM), the dextrorotatory isomer of 3-hydroxy-N-methylmorphinan, is the main ingredient in a number of widely available, over-the-counter antitussives. Initial studies (Bornstein 1968) showed that it possessed no respiratory suppressant effects and no addiction liability. Subsequently, however, several articles reporting abuse of this drug have appeared in the literature. The drug is known to cause a variety of acute toxic effects, ranging from nausea, restlessness, insomnia, ataxia, slurred speech and nystagmus to mood changes, perceptual alterations, inattention, disorientation and aggressive behavior (Rammer et al 1988; Katona and Watson 1986; Isbell and Fraser 1953; Devlin et al 1985; McCarthy 1971; Dodds and Revai 1967; Degkwitz 1964; Hildebrand et al 1989). There have also been two reported fatalities from DM overdoses (Fleming 1986). However, there are no reports describing the effects of chronic abuse. This report describes a case of cognitive deterioration resulting from prolonged use of DM.

Adult↗

[The approach of the letterbox: a model of sex education in a traditional society].

The present article describes a new approach for imparting sex-education to adolescents in a conservative and orthodox society like India. The initial community resistance to sex education was overcome by conducting a survey on the sex behaviour of adolescents. Contrary to popular belief and notions, the survey proved that some adolescents are sexually active and that they are not adequately equipped to prevent and protect themselves against sexually transmitted diseases, AIDS and unwanted pregnancies. The new model is essentially based on the team/group approach and utilises a group of trained and motivated teachers in schools to impart sex education to a group of students. The students' response to this approach has been heartening and encouraging.

Adolescent↗

Laparoscopic cholecystectomy: laboratory predictors of choledocholithiasis.

Liver function tests (LFTs) are most often employed to select patients for preoperative endoscopic retrograde cholangiography (ERC) and therapeutic sphincterotomy. Although ERC accurately detects CBD stones, the associated financial costs and potential morbidity argue against its indiscriminate use. We analyzed the value of LFTs to predict CBD stones in patients treated by laparoscopic cholecystectomy (LC). CBD stones were identified in 41 of 660 patients (6.2%) treated by LC during the study period (January 1991 to May 1993). CBD stones were identified by preoperative ERC in 19 of 33 patients (57.6%); by operative cholangiography in 18 of 289 patients (6.2%), and by postoperative ERC in 4 patients. In patients with CBD stones, there was a significant difference in alkaline phosphatase, total bilirubin, SGPT, and SGOT (P < 0.001). The positive predictive value (PPV) of a value > normal at admission was 5%-19%; and immediately before operation was 9%-36%. The PPV of a value > 2X normal was 30%-47%. Alkaline phosphatase and total bilirubin were independent predictors of CBD stones. If both were greater than twice normal, there was a 55 per cent incidence of CBD stones. Our analysis suggests that patients with greater than twice normal liver function tests have a sufficient incidence of CBD stones to warrant ERC. Patients without both these criteria should be managed by laparoscopic CBDE, with postoperative endoscopic stone retrieval for the failures of laparoscopic CBDE.

Adult↗

Parent and teacher ratings of attention-deficit hyperactivity disorder symptoms: implications for case identification.

This study was designed to evaluate the relationship between the DSM-III criteria for attention-deficit deficit disorder with hyperactivity (ADDH) and the DSM-III-R criteria for attention-deficit hyperactivity disorder (ADHD). Seventy-two children from an inner-city elementary school were evaluated using parent and teacher ratings on a scale consisting of the symptoms of DSM-III-R ADHD and oppositional-defiant disorder and DSM-III ADDH. Each child was also assessed using a psychometric test battery designed to examine cognitive function, attention, and activity level. Teacher ratings identified more children as DSM-III-R ADHD than DSM-III ADDH. Among these ADHD children, those who also met the ADDH criteria missed more targets on a continuous performance test (CPT) and were rated more overactive than controls. They also had a greater likelihood of being rated ADHD by parents. Children rated as meeting criteria for DSM-III-R ADHD, but not DSM-III ADDH, were not substantially different from controls on teacher ratings of overactivity, CPT performance, or parent ratings of ADHD, which raises questions regarding the nature and severity of the pathology in this group.

Attention↗

Advanced glycosylation endproduct-specific receptors on human and rat T-lymphocytes mediate synthesis of interferon gamma: role in tissue remodeling.

During normal aging and in chronic diabetes the excessive accumulation of reactive glucose-protein or glucose-lipid adducts known as advanced glycosylation endproducts (AGEs) has been shown to induce tissue dysfunction, in part through interaction with AGE-specific receptors on monocyte/macrophages and other cells. Recognizing that circulating lymphocytes trafficking through tissues interact with tissue AGEs, we searched for the expression of AGE-binding sites on peripheral blood T lymphocytes. Resting rat and human T cells bound 125I-AGE-albumin with an affinity of 7.8 x 10(7) M-1, whereas, after stimulation with phytohemagglutinin (PHA) for 48 h, binding affinity increased to 5.8 x 10(8) M-1. Flow cytometric analysis of resting rat T cells using polyclonal antibodies raised against rat liver AGE-binding proteins (p60 and p90) revealed the constitutive expression of both immunoreactivities. The number of resting CD4+ and CD8+ T cells positive for anti-p60 antibody binding (34.2 and 58.5%, respectively) increased to 92 and 90% of cells after 48-h stimulation with PHA. Exposure of PHA-activated T lymphocytes to AGE-albumin enhanced expression of interferon gamma (IFN-gamma) mRNA 10-fold and induced greater elaboration of the mature protein than did exposure to unmodified protein or PHA treatment alone. These data indicate that T cells contain an inducible system of surface receptors for AGE-modified proteins, and that receptor occupancy is linked to lymphokine production. This T cell AGE-receptor system might serve to target lymphocytes to AGE-rich tissues and involve them in the regulation of tissue homeostasis either by assisting in macrophage-dependent clearance of AGE-proteins, or by exerting direct antiproliferative action on mesenchymal cells. Under conditions of excessive AGE-protein and AGE lipid accumulation (e.g., aging and diabetes), enhanced production of AGE-induced IFN-gamma may accelerate immune responses that contribute to tissue injury.

Animals↗

Therapeutic factors influencing the cosmetic outcome and late complications in the conservative management of early breast cancer.

PURPOSE: To investigate the impact of clinical and physical parameters on the cosmetic result and complications, in cancer breast treated with conservative surgery and definitive irradiation. METHODS AND MATERIALS: Between October 1980 and December 1990, 289 patients were treated with lumpectomy and/or axillary dissection, radical irradiation with or without adjuvant therapy. The radiation therapy technique consisted of external beam therapy followed by an Ir-192 implant or electron beam boost. Univariate and multivariate analysis were used to evaluate the correlation between multiple factors affecting the cosmetic outcome and the complications. RESULTS: Of 289 patients, cosmesis was evaluable in 285 and recorded as excellent to good in 226 (79%), fair in 35 (12%), and poor in 24 (9%). On multivariate analysis of these results, a high dose per fraction (p = .0018), and use of electrons as boost to the tumor bed (p = .001) were found to be significant. When patients boosted with electrons were excluded, a high boost dose (p = .0433) was also found significant. Fifteen (5%) patients developed severe late radiation sequelae and 14 (5%) moderate or severe arm edema. On multivariate analysis only dose per fraction of 2.5 Gy (p < .0001) and higher boost doses (p = .017) were significant. CONCLUSION: In 289 patients of early breast cancer treated with conservative surgery and radical irradiation, multivariate analysis suggests that higher dose per fraction with teletherapy and higher brachytherapy boost dose adversely affect cosmesis and contribute to the late complications.

Adult↗

Sulfite inhibits oxalate production from glycolate and glyoxylate in vitro and from dichloroacetate infused i.v. into male rats.

The effect of sulfite on oxalate production from glycolate and glyoxylate was investigated in an in vitro assay system using rabbit muscle LDH and rat liver 35-60% ammonium sulfate fraction as enzymes. A > or = 50% inhibition in oxalate production was observed at sulfite to glyoxylate ratio of 0.4. LDH activity (change in A340 nm) was inhibited by > or = 40% at sulfite to glyoxylate ratio of 0.5. Male Sprague-Dawley rats fasted for 24 h and infused with dichloroacetate (150 mg/rat/h, iv, n = 6), without and with sodium sulfite (150 mg/rat/h, n = 6) excreted oxalate in urine, respectively, at the rate of 1.13 +/- 0.29 and 0.61 +/- 0.09 mumol/h/100 g body wt, showing a nearly 50% reduction due to sulfite. The present report demands further experimentation to define the role of sulfite as an intracellular modulator of oxalate production.

Alcohol Oxidoreductases↗

A linkage map of human chromosome 21:43 PCR markers at average intervals of 2.5 cM.

A genetic linkage map of human chromosome 21q (HC21q) containing 43 markers genotyped by the polymerase chain reaction in the CEPH pedigrees is presented. The markers placed on this map are highly polymorphic with an average heterozygosity of 61%. The average interval size of the markers localized at 1000:1 odds is 2.5 cM. The map has a total length of 65.5 cM, with male and female lengths of 47.7 and 83.3 cM, respectively. The genotypes used in the construction of this map were subjected to rigorous error checking, which is reflected in the shorter map length compared to previous maps; the estimated error rate in genotyping is less than 0.04%. As noted in previous linkage maps there is increased recombination in females on proximal HC 21q and in the male in a region near the telomere. This map of HC 21 represents a highly informative and dense meiotic linkage map and will be useful in linking disease phenotypes to loci on this chromosome.

Chromosome Mapping↗

Placental and ovarian hormones in anembryonic pregnancy.

The circulating levels of human chorionic gonadotrophin (HCG), pregnancy-associated plasma protein-A (PAPP-A), Schwangerschaft protein 1 (SP-1), oestradiol and progesterone were measured in 81 pregnant patients between 4 and 11 weeks gestation, following in-vitro fertilization and embryo transfer. The patients were divided as follows: singleton anembryonic pregnancies, n = 22; singleton pregnancies which spontaneously aborted following the demonstration of fetal heart activity, n = 7; and normal singleton pregnancies, n = 52. The levels of all substances measured were significantly reduced in women with anembryonic compared to those with singleton pregnancies which proceeded to term. The serum levels of SP-1, weeks 6-8 (P < 0.01); HCG, weeks 6-8 (P < 0.05); oestradiol, weeks 5-8 (P < 0.05) and progesterone, weeks 6-8 (P < 0.05), were lower in anembryonic pregnancies than in those of pregnancies which spontaneously aborted. These differences may be a reflection of the fact that miscarriage, after the demonstration of fetal heart activity, represents fetal demise at a later stage in pregnancy. In anembryonic pregnancies, significant associations were found between HCG and both oestradiol and progesterone levels from weeks 6 and 8, suggesting that in the absence of an embryo, HCG is the prime determinant of steroid synthesis by the corpus luteum.

Abortion, Spontaneous↗